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ATG-Fresenius inhibits blood circulating cell proliferation in a dose-dependent manner: an experimental study.

Abstract：

INTRODUCTION:Antithymocyte globulin (ATG)-Fresenius (Neovii-Biotech, Graefelfing, Germany), a highly purified rabbit polyclonal antihuman T-lymphocyte immunoglobulin resulting from immunization of rabbits with the Jurkat T-lymphoblast cell line, is currently used for the prevention of acute rejection in patients receiving solid organ transplants. Our aim was to investigate the in vitro activity of ATG-Fresenius regarding the proliferation of peripheral blood mononuclear cells (PBMCs), an important mechanism of rejection after solid organ transplantation. METHODS:PBMCs were isolated from 6 healthy donors. Proliferation was assayed using [(3)H] thymidine incorporation. For analysis of mitogen-stimulated proliferation, the PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius in the absence/presence of 40 μg/mL phytohemagglutinin. For analysis of the mixed lymphocyte reaction, PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius for 3 days. On day 3, PBMCs (stimulator cells) from allogeneic donors were incubated with 25 μg/mL mitomycin C. The responder cells (preincubated with ATG-Fresenius) were then cultured at 37°C with the stimulator cells for 6 days. Groups were compared using ANOVA and the Tukey-Kramer multiple comparison test. RESULTS:Preincubation of PBMCs with ATG results in concentration-dependent inhibition of phytohemagglutinin-stimulated proliferation. The effect was more pronounced after 2 and 3 days of treatment with ATG compared with 1 day. There was a concentration-dependent decrease in the mixed lymphocyte reaction-induced proliferation (up to 80%) at ATG-Fresenius concentrations as low as 0.05 to 0.5 μg/mL. No further effect on proliferation at ATG-Fresenius concentrations of 0.5 to 50 μg/mL was seen, and higher concentrations (>100 μg/mL) totally inhibited proliferation. CONCLUSIONS:Our in vitro results provide more evidence of the beneficial effect of ATGs in the early phase of solid organ transplantation, by reducing effector cell proliferation.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Werner I,Seitz-Merwald I,Kiessling AH,Kur F,Beiras-Fernandez A

doi

10.1016/j.transproceed.2014.07.016

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

3000-3

issue

9

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(14)00519-3

journal_volume

46

pub_type

杂志文章

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